首次批准比索洛尔治疗心力衰竭

默克ＫＧａＡ公司生产的β阻滞剂比索洛已被批准在其第一市场瑞典用于治疗心力衰竭。有望很快得到欧洲方面的批准。比索洛尔早已被广泛用于治疗高血压及心绞痛。１９９８年其销售额为３．７亿美元,分析家认为２００１年可能达６亿美元。比索洛尔是继史克－比彻姆／罗氏公司的卡维地洛之后第二个β阻滞剂治疗心力衰竭的产品。比索洛尔的适应证是以ＣＩＢＩＳ－２试验结果为基础的,去年首次报道同安慰剂相比,比索洛尔可降低心力衰竭的死亡率。第三个β阻滞剂现在也表现出治疗心力衰竭的效果,今年早期一项大规模ＭＥＲＩＴ试验报道死亡率的…     

比索洛尔和美托洛尔治疗223例慢性充血性心力衰竭的疗效比较

目的:比较比索洛尔和美托洛尔治疗慢性充血性心力衰竭的疗效。方法:233例慢性充血性心力衰竭病人随机分为比索洛尔组和美托洛尔组。比索洛尔组(116例)每日口服比索洛尔2.5～10mg,美托洛尔组(117例)每日口服美托洛尔25～100mg。共治疗2a。结果:比索洛尔组临床总有效率为72.4％,美托洛尔组临床总有效率为70.1％(临床心功能与用药前相比均P<0.01)。2组用药后超声心动图测得的左室收缩功能均明显改善(P<0.01)。2组死亡率、心血管疾病死亡率及心血管疾病住院次数无明显差别。结论:比索洛尔和美托洛尔均对治疗慢性充血性心力衰竭有效。     

比索洛尔治疗慢性充血性心力衰竭的临床分析

目的研究比索洛尔治疗慢性充血性心力衰竭(CHF)的临床观察。方法比索洛尔与强心、利尿剂等配合使用治疗CHF,判定比索洛尔是否明显改善CHF患者的心功能及提高患者的生活质量。结果采用比索洛尔与强心、利尿扩血管等药物联合使用,比索洛尔治疗组有效率(95.83%)明显高于常规治疗组(77.08%)(P<0.05)。结论常规抗心力衰竭治疗基础上加用比索洛尔治疗能提高疗效,显著改善CHF患者的心功能,降低患者的病死率。     

IL －33／ST2信号通路在比索洛尔治疗舒张性心力衰竭中的作用

目的：观察IL－33／ST2信号通路在比索洛尔治疗舒张性心力衰竭（ DHF）中的作用。方法24只舒张性心力衰竭老鼠随机分为对照组（n＝12）及比索洛尔组（n＝12）,分别用蒸馏水及比索洛尔溶液治疗,疗程6周。观察2组的左室压力、左室充盈时间（ LVFT）、左室舒张压、等容收缩期左心室内压最大上升速率及心肌细胞ST2蛋白及血清肿瘤坏死因子（ TNF－α）的浓度。结果比索洛尔组小鼠左室收缩压、左心室平均压均显著低于对照组（P＜0.05）,但2组左室舒张压差异无统计学意义（ P＞0.05）。比索洛尔组等容收缩期左心室内压最大上升速率显著高于对照组（ P＜0.05）;等容舒张期左心室内压最大下降速率显著低于对照组（P＜0.05）,而左室充盈时间2组差异无统计学意义（P＞0.05）。比索洛尔组IL－33蛋白表达显著降低（ P＜0.05）,但ST2表达量和血清中TNF－α浓度2组差异均无统计学意义（ P＞0.05）。结论比索洛尔可有效降低舒张性心力衰竭小鼠的左室血压,改善左心室顺应性,其机制可能与心肌细胞内IL－33蛋白表达量显著减少有关。     

美托洛尔和比索洛尔治疗慢性心力衰竭患者120例的疗效观察

目的观察美托洛尔和比索洛尔治疗慢性心力衰竭的疗效。方法选取2010年1月～2011年12月入院治疗的120例心力衰竭患者,应用美托洛尔治疗,设为美托洛尔组,同样选取同时期入院的应用比索洛尔治疗的120例心力衰竭患者,设为比索洛尔组。观察比较两组的疗效。结果比索洛尔组120例患者中,显效51例（42.50%）,好转57例（47.50%）,无效12例（10.00%）,总有效率为90.00%;美托洛尔组120例患者中,显效57例（47.50%）,好转45例（37.50%）,无效18例（15.00%）,总有效率为85.00%。两组患者治疗后均能有效降低心率、舒张压和收缩压,两组在控制血压方面差异无统计学意义（P〉0.05）,但在控制心率方面比索洛尔组优于美托洛尔组（P〈0.05）。结论美托洛尔和比索洛尔均能安全有效地改善慢性心力衰竭患者的心脏功能,但是比索洛尔在耐受性、减慢心率等方面比美托洛尔疗效更为优良确切。     

比索洛尔用于治疗慢性心力衰竭

比索洛尔是一种高选择性的β1-肾上腺素能受体阻滞剂，慢性心力衰竭患者服用比索洛尔可提高左心室收缩功能。两项主要的多中心、随机、双盲、安慰剂对照临床研究表明，比索洛尔与血管紧张素转化酶抑制剂(ACEI)类药物和利尿剂合用，可降低慢性心力衰竭患者的死亡率及因各种原因所致的住院率，同时，具有较好的药物经济学特性。因此，比索洛尔与ACEI类药物和利尿剂合用可作为治疗中、重度稳定型慢性心力衰竭的常规用药。     

比索洛尔在慢性心力衰竭治疗中应用分析

目的：探讨比索洛尔在慢性心力衰竭治疗中的应用。方法：将2008年1月～2010年6月诊治的216例慢性心力衰竭患者随机分为常规治疗组106例和比索洛尔组110例。常规治疗组针对性原发疾病治疗及应用血管紧张素转化酶抑制剂、血管紧张素受体拮抗剂、利尿剂、醛固酮拮抗剂、血管扩张剂（如硝酸甘油、硝普钠等）。比索洛尔组采用常规治疗联合比索洛尔治疗。观察两组的临床疗效。结果：常规治疗组总有效率为72.64%,比索洛尔组总有效率为92.72%,两组总有效率比较,差异有统计学意义（P〈0.01）。结论：在慢性心力衰竭治疗过程中应用β受体阻滞剂比索洛尔,有减慢心率、降低心肌耗氧、抑制心室重构,长期应用安全可靠、副作用小等优点。     

比索洛尔与卡维他洛治疗慢性心力衰竭的疗效观察

目的对比索洛尔与卡维他洛治疗慢性心力衰竭的疗效进行观察。方法慢性心力衰竭患者176例,随机分为A组和B组,各88例。在常规治疗基础上,A组患者采用比索洛尔治疗,B组患者采用卡维他洛进行治疗。治疗6个月后对两组患者治疗的总有效率、左心室射血分数(LVEF)、血压及心率进行比较。结果经过了6个月的治疗后,A组慢性心力衰竭患者的总有效率为86.4%,心率降低更加显著;B组的总有效率为83.0%,A组血压降低更为明显(P<0.05)。结论比索洛尔与卡维他洛这两种药物在治疗慢性心力衰竭时治疗效果都很好。其中比索洛尔具有更好的降低心率的效果,而卡维他洛则具有更佳的降低血压的效果。     

小剂量比索洛尔治疗充血性心力衰竭临床观察

目的 探讨小剂量比索洛尔对充血性心力衰竭（ＣＨＦ）病人的治疗效果。方法 ３０例ＣＨＦ病人先用传统常规治疗使心力衰竭得到初步控制后,口服比索洛尔１．２５ｍｇ,１ｄ１次,１周后每１０日增加１．２５ｍｇ,至增加至５ｍｇ,治疗时间不少于３个月。结果 小剂量比索洛尔治疗ＣＨＦ改善心功能有效率为９３％。结论 比索洛尔治疗ＣＨＦ疗效好,副作用少,适合于中度衰伴心动过速、高血压和心绞痛心肌缺血的ＣＨＦ病人。     

小剂量比索洛尔治疗肺源性心脏病心力衰竭疗效观察

目的 探讨小剂量比索洛尔在慢性阻塞性肺病中心力衰竭的疗效及对肺功能的影响.方法 肺心病患者40例,随机分为治疗组和对照组各20例.治疗组在常规治疗的基础上加用小剂量比索洛尔口服,疗程4～6周,对比分析疗效及治疗前后血气变化.结果 应用比索洛尔组治疗慢性肺源性心脏病心力衰竭,心功能改善明显;两组治疗前后心率变化差异有非常显著性（P＜0.001）;观察组治疗前后血PO2、PCO2、SaO2均无明显改变（P＞0.05）.结论 小剂量比索洛尔治疗肺源性心脏病心力衰竭疗效显著,且无气道阻力增高副作用,是心力衰竭的治疗方法之一特别是经常规治疗效果不佳者.     

Bisoprolol: a review of its use in chronic heart failure

Bisoprolol is a highly selective beta(1)-adrenoceptor antagonist. Administration of bisoprolol to patients with chronic heart failure is associated with increases in left ventricular function and reductions in heart rate; increases in heart rate variability are also seen. Two major randomised, double-blind, placebo-controlled, multicentre trials have examined the clinical efficacy of bisoprolol in combination with ACE inhibitors and diuretics in patients with stable chronic heart failure (New York Heart Association class III or IV): the Cardiac Insufficiency Bisoprolol Study (CIBIS; n = 641) and CIBIS II (n = 2 647). All-cause mortality (primary endpoint) was significantly lower in bisoprolol than in placebo recipients in CIBIS II (11.8 vs 17.3%) and was reduced by bisoprolol regardless of dosage. All-cause mortality was also lower in CIBIS (16.6 vs 20.9%) although the difference did not achieve statistical significance. In a meta-analysis of CIBIS and CIBIS II (n = 3 288), a relative reduction of 29% in the incidence of all-cause mortality was seen in bisoprolol versus placebo recipients; this analysis also demonstrated that bisoprolol reduces mortality in patients with chronic heart failure regardless of aetiology or severity. In CIBIS II, there were significantly fewer cardiovascular deaths, admissions to hospital for any reason, or cardiovascular deaths or cardiovascular hospitalisations (combined endpoint) in bisoprolol, compared with placebo, recipients (secondary endpoints). Compared with standard treatment alone, the addition of bisoprolol was a cost-effective option in chronic heart failure in UK, French, German and Swedish pharmacoeconomic studies. Bisoprolol is generally well tolerated in patients with chronic heart failure. In CIBIS II, adverse events occurring more commonly in bisoprolol than placebo recipients, regardless of causal relationship with the study medication, included dizziness, bradycardia, hypotension and fatigue. Bisoprolol recipients were less likely than placebo recipients to experience worsening of heart failure, dyspnoea or tachycardia. In both CIBIS and CIBIS II there was no significant difference between bisoprolol and placebo recipients in the incidence of permanent treatment withdrawal. In conclusion, adding the highly selective beta(1)-blocker bisoprolol to a treatment regimen comprising an ACE inhibitor and a diuretic significantly improves survival in patients with stable chronic heart failure and reduces the need for hospitalisation. The use of bisoprolol in this disorder is generally well tolerated and is cost effective. Thus, bisoprolol should be considered a standard treatment option when selecting a beta-blocker for use in combination with ACE inhibitors and diuretics in patients with stable, moderate to severe chronic heart failure.     

比索洛尔治疗充血性心力衰竭临床观察

目的:观察比索洛尔治疗充血性心力衰竭疗效。方法:54例充血性心力衰竭患者,在常规治疗病情基本稳定的基础上,随机分为对照组25例和治疗组29例。对照组给予地高辛、利尿剂、血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体拮抗剂(ARB)治疗;治疗组在常规治疗的基础上,给予比索洛尔治疗,比索洛尔从1.25 mg Qd开始,缓慢递增,至10 mg Qd或最大耐受剂量,随访时间为12周。治疗前后分别进行心功能(NYHA)分级、血压、心率测定、超声心动图检查并做统计学处理。结果:与治疗前相比:对照组心功能分级改善(P<0.05),左室射血分数(LVEF)增加(P<0.05);治疗组心功能分级显著改善(P<0.01),LVEF和左室短轴缩短率(FS)明显增加(P<0.01),左室舒张末期内径(LVDd)显著缩短(P<0.01),左室收缩末期内径(LVDs)缩短(P<0.05)。两组治疗后相比,比索洛尔组LVEF、FS较常规组改善更为显著(P<0.01)。结论:比索洛尔在心衰常规治疗基础上治疗充血性心力衰竭有良好的疗效,能显著改善心功能,改善衰竭左室的重构。     

比索洛尔和卡维地洛治疗慢性心力衰竭疗效比较

目的分析比较比索洛尔和卡维地洛治疗慢性心力衰竭的疗效。方法将2007年1月至2008年1月收治的78例慢性心力衰竭患者随机分为比索洛尔组40例和卡维地洛组38例,比索洛尔组在继续常规抗治疗的基础上,给予口服比索洛尔治疗;卡维地洛组在继续常规抗治疗的基础上,给予13服卡维地洛治疗。所有患者治疗前后均行超声心动图检查,测量LVEF和左心室舒张末期容积（LVEDV）、左心室收缩末期容积（LVESV）,测量血压和心率。治疗一年后,比较两组患者各项指标。结果索洛尔组和卡维地洛组治疗前后超声心动图指标LVEDV、LVESV、LVEF、血压、收缩压和舒张压均具有显著性差异（P〈0．01）;而治疗后两组组间比较只有LVEF比较有显著性差异（P〈0．05）,其余各项指标均不存在显著性差异（P〉0．05）,差异无统计学意义。结论应用比索洛尔和卡维地洛治疗慢性心力衰竭患者,疗效相似,均能显著改善心力衰竭患者的心功能,临床可以推广应用。     

比索洛尔与卡托普利联合治疗慢性心力衰竭的临床效果

目的探讨比索洛尔与卡托普利联合应用治疗慢性心力衰竭的效果。方法60例慢性心力衰竭患者随机分为试验组34例和对照组26例。对照组给予常规纠正心力衰竭治疗,试验组在对照组基础上加用比索洛尔与卡托普利口服,疗程14d,观察2组血压、心率、脉搏变化情况并随访4个月。结果2组的心率、脉搏、血压、再入院例数及再入院时间比较差异均有统计学意义（P〈0.05）。试验组因心脏事件再入院率低于对照组,再住时间短于对照组,差异均有统计学意义（P〈0.05）。结论尽早采用比索洛尔与卡托普利联合治疗慢性心力衰竭,有益于改善患者的临床症状,促进心功能恢复,减少患者再入院率,减轻其经济负担。     

Assessment of beta-adrenoceptor selectivity of a new beta-adrenoceptor antagonist, bisoprolol, in man

Bisoprolol is a new beta-adrenoceptor antagonist which has shown beta-adrenoceptor selectivity in studies in isolated tissues. Bronchial and cardiac beta-adrenoceptor blockade were assessed in eight normal subjects before and after oral ingestion of placebo, bisoprolol 20 and 40 mg, metoprolol 200 mg and propranolol 80 mg in random order. Bronchial beta-adrenoceptor blockade was assessed as the displacement of the bronchodilator dose-response curve to inhaled isoprenaline after each beta-adrenoceptor blocking drug compared to placebo and expressed as the dose ratio. Bronchodilatation was measured as change in specific airway conductance (sGaw) in the body plethysmograph. Cardiac beta-adrenoceptor blockade was assessed as the percentage reduction in exercise heart rate during the fifth minute of exercise at 70% of the subject's maximum work rate. Bisoprolol 20 and 40 mg caused a 24 and 25% reduction in exercise heart rate respectively, compared to 26% with metoprolol 200 mg and 20% with propranolol 80 mg. The dose ratios for the airway dose-response curves for the four beta-adrenoceptor blocking drugs were 1.04 and 3.4 for bisoprolol 20 and 40 mg, 1.4 for metoprolol 200 mg and 30 for propranolol 80 mg. Both doses of bisoprolol produced considerably less bronchial beta-adrenoceptor blockade than propranolol 80 mg despite causing a greater reduction in exercise heart rate. Bisoprolol 20 mg caused a similar amount of bronchial beta-adrenoceptor blockade and a similar reduction in exercise heart rate as metoprolol 200 mg, confirming that it is cardio-selective in man.     

比索洛尔对充血性心力衰竭患者血浆脑钠肽水平的影响

目的探讨比索洛尔对充血性心力衰竭患者血浆脑钠肽（BNP）水平的影响。方法对84例慢性充血性心力衰竭患者在常规抗心衰治疗的基础上应用比索洛尔,2．5mg／a,治疗2周后根据患者心功能恢复情况调整5—10mg／d,维持治疗3个月,观察患者治疗前后心率、血压、射血分数的变化,并应用ELISA检测检测者血BNP水平变化。结果84例患者中,心功能：Ⅰ级14例,Ⅱ级24例,Ⅲ级28例,Ⅳ级18例,BNP水平分别为：（112．56±14．79）ng／L、（242．69±37．35）ng／L、（452．57±49．66）ng／L、（882．75±163．27）ng／L,随着心功能变差BNP水平逐渐增高,两两比较,差异均有统计学意义（t=4．241、4．573、4．074、7．328,均P〈0．01）。经治疗后,显效28例（33．3％）,有效41例（48．8％）,无效15例（17．9％）,有效率82．1％;治疗后患者心率减慢、血压降低、左室射血分数较治疗前明显升高（t=3．585、3．245、3．347,均P〈0．05）,治疗后BNP水平明显降低（（t=4．876,P〈0．01）。结论BNP水平可以反映充血性心力衰竭患者心功能水平,应用比索洛尔治疗充血性心力衰竭可以改善患者心功能,降低患者BNP水平。     

Pharmacodynamic profile of the selective beta 1-adrenoceptor antagonist bisoprolol

The pharmacodynamic activity of (+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2- propranol- hemifumarate (bisoprolol, EMD 33 512) has been investigated under in vitro and in vivo conditions. Bisoprolol was found to be an effective beta-adrenoceptor antagonist, the pA2 values determined against isoprenaline in guinea pig atria and tracheal muscle being 7.45 and 6.41, respectively. Thus, the selectivity ratio of bisoprolol in favour of beta 1-adrenoceptors is 11. Inhibition of the isoprenaline-induced tachycardia in guinea pigs indicated a long duration of action for bisoprolol. The compound was devoid of intrinsic sympathomimetic activity as shown by the lack of effect on heart rate in anaesthetized and reserpine pretreated rats. Studies in rabbits and guinea pigs revealed a local anaesthetic activity of bisoprolol at high concentrations. Bisoprolol protected the hearts of anaesthetized dogs against the sequelae of intermittent coronary occlusions, as judged by the reduction of the ST-segment elevation in the epicardial ECG. Bisoprolol exerted a blood pressure lowering effect in conscious renal hypertensive dogs after oral administration of 30 micrograms/kg. There was no indication of any action on the CNS in monkeys following an oral dose of up to 8 mg/kg.     

Cardiopulmonary effects of celiprolol and bisoprolol in serotonin-infused cats

The effects of celiprolol and bisoprolol on cardiopulmonary function in serotonin-infused cats were compared. Celiprolol reversed the bronchoconstrictive effect of serotonin at doses greater than or equal to 1.0 mg/kg. Also, decreases in mean arterial pressure and heart rate were noted after administration of 3-10 and 10 mg/kg celiprolol, respectively. In contrast, bisoprolol tended to induce bronchoconstriction. Reductions in mean arterial pressure and heart rate were observed with 1 or 3 mg/kg. Bisoprolol administration at 10 mg/kg was lethal. The unique ability of celiprolol to induce bronchodilation enhances its therapeutic potential.     

比索洛尔治疗冠心病合并COPD高龄患者对肺功能的影响

目的:根据比索洛尔在治疗冠心病合并慢性阻塞性肺疾病(COPD)高龄患者中的应用状况,分析其对肺功能的影响,为临床治疗提供参考。方法:对照组45例高龄冠心病合并COPD患者给予常规治疗,治疗组51例在常规治疗的基础上服用比索洛尔,疗程4周。观察治疗组与对照组患者的临床症状、心电图、心率及治疗前后VC、TV、FVC、FEV1、FEV1%、MMF等肺功能数值的变化。结果:比索洛尔治疗组在临床症状、心电图、降低心率等指标方面明显优于对照组(P<0.05),治疗前后两组患者肺功能均无明显变化。结论:比索洛尔对冠心病合并COPD的高龄老年患者的肺功能无明显影响,且药物不良反应少。     

比索洛尔在老年慢性肺源性心脏病中的应用

目的观察比索洛尔对老年慢性肺源性心脏病患者症状、体征、心率、血压、肺功能、心功能、血糖、血脂的影响。方法选择老年慢性肺源性心脏病患者68例,在原有治疗基础上加用比索洛尔。用药期间观察临床症状、肺部啰音,用药前、用药后2周、用药后4周分别行动态血压、肺功能、超声心动图检查以及肝肾功能、血糖、血脂等指标。结果临床总有效率为82.4%。用药后2周、4周观察心率和血压均较用药前明显下降（P〈0.05）;且无明显不良反应。结论比索洛尔应用于慢性肺源性心脏病,疗效较好,且无明显不良反应,值得推广应用。